2008 Barcelona - European Society of Human Genetics

Clinical genetics
The cause of this disorder is unknown . All cases have been sporadic
events in the otherwise normal families . It is most likely caused by a
somatic mutation of a gene that is lethal when occurring in the nonmosaic
state .
We report on a sporadic case of two years old boy in which Proteus
Syndrome is diagnosis because of a large haemangioma in the right
hemi chest and the upper limb . He has also a macrodactyly of the left
thumb, hemihypertrophie . He has also a multiple soft subcutaneous
swellings over the chest and the abdomen .
P01.351
Identification of PSEN1Δ9 mutation in mexican families with
spastic paraparesis and presenil dementia
G. Castañeda-Cisneros 1,2 , D. García-Cruz 3 , C. Moran-Moguel 1 , S. Gutiérrez-
Rubio 1 , M. López-Cardona 3 , I. Dávalos-Rodríguez 4 , R. Rosales-Gómez 1 , F.
Jiménez-Gil 5 , P. Nava-Rodríguez 4 , M. Macías 5 , J. Sánchez-Corona 1 ;
1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente,
Instituto Mexicano del Seguro Social, Guadalajara, Mexico, 2 Departamento
de Neurocirugía, Hospital de Especialidades, Instituto Mexicano del
Seguro Social, Guadalajara, Mexico, 3 Instituto de Genética Humana, Universidad
de Guadalajara, Guadalajara, Mexico, 4 División de Genética, Centro de
Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social,
Guadalajara, Mexico, 5 Departamento de Neurología, Hospital de Especialidades,
Instituto Mexicano del Seguro Social, Guadalajara, Mexico.
Spastic paraparesis and early-onset dementia (also known as earlyonset
familial Alzheimer disease-3) is rare, and 26 families have been
worldwide described; in most of them several mutations in PSEN1
included point mutations (exons 3, 4, 7, 8 y 12), insertions (exon 3)
and deletions (exons 4, 9, 12) that have been identified. Our aim is to
detect the PSEN1Δ9 mutation related with high frequency and severity
. In Mexico there are not familial reports with this disease, therefore
it is unknown if previously described mutations are present in these
families .
In this study we described eight families with clinical signs that correlated
with spastic paraparesis and early-onset dementia . They showed
an autosomal dominant inheritance with variable expressivity . Affected
subjects per family are 2 to 6 with mean onset age of 45 .1 years and
sex ratio of 1/0 .76 .
Molecular analysis demonstrated a PSEN1Δ9 mutation in eight affected
subjects and in two non-affected (33 and 36 years old), 34 .78%
and 6.06% of total amount respectively. At least it was identified in
one affected subject out of six studied families . It was not possible to
conclude that PSEN1Δ9 mutation itself explains the presence of this
phenotype in Mexican families .
P01.352
Primary pulmonary vein stenosis and lymphatic anomalies: a
new syndrome?
I. van de Laar, I. Frohn-Mulder, M. Dalinghaus, R. de Krijger, M. Husen-Ebbinge,
A. M. Bertoli-Avella, M. Wessels;
Erasmus Medical Center, Rotterdam, The Netherlands.
Primary pulmonary vein stenosis is a rare congenital vascular malformation
with a high mortality rate . It is characterized by obstruction
of one or multiple pulmonary veins. Most patients present in the first
year(s) of life with failure to thrive, dyspnoea, and recurrent pneumonias
. Later pulmonary hypertension, pulmonary oedema and haemoptysis
develop . Most patients die during infancy since there are no
adequate therapeutic options . So far only sporadic cases have been
described . The aetiology of the disease is unknown and many possible
underlying pathologic mechanisms have been described .
We present a consanguineous Turkish family with four affected siblings
(three males and one female) of healthy parents. The first child
died at 16 months due to progressive pulmonary vein stenosis . The following
two sibs presented prenatally with cystic hygroma and mild skin
oedema . Chromosome analysis was normal . At birth cardiac evaluation
was normal but both developed severe and progressive stenosis
of the pulmonary veins in the following months of life . Both died before
the age of 8 months due to restenosis of the pulmonary veins after surgical
intervention . The fourth pregnancy was terminated due to cystic
hygroma and severe hydrops .
These data provide evidence for an autosomal recessive form of primary
pulmonary vein stenosis associated with lymphatic anomalies
and hydrops . We are performing genome wide linkage studies in this
family to locate the gene for primary pulmonary vein stenosis . This
syndrome might be underdiagnosed due to post- and prenatal lethality
.
P01.353
Quadrupedal Locomotion and cerebellar Hypoplasia caused
by mutations in the Very Low Density Lipoprotein Receptor
(VLDLR) Gene
S. Türkmen 1 , K. Hofmann 1 , D. Aruoba 2 , N. Humphrey 3 , S. Mundlos 1,4 ;
1 Charité Virchow-Klinikum, Berlin, Germany, 2 Valikonogi Nisantasi, Istanbul,
Turkey, 3 Centre for Philosophy of Natural and Social Science, London School
of Economics, London, United Kingdom, 4 Max Planck Institut für Molekulare
Genetik, Berlin, Germany.
The cerebellum is the primary motor coordination centre of the central
nervous system . Lesions or congenital defects of the cerebellum
cause incoordination of the muscles resulting in irregular gait and falling
. Recently, we reported a large family with cerebellum hypoplasia
and quadrupedal locomotion as a recessive trait, which we mapped to
chromosome 17p13 .
We identified one additional family with the same condition and
mapped the underlying gene to a 14-centimorgan interval on chromosome
9ptel using a genome wide linkage approach . Sequencing of
candidate genes identified a homozygous frameshift mutation in the
Very Low Density Lipoprotein Receptor (VLDLR) gene in all affected
individuals . The association of cerebellar hypoplasia with mutations in
VLDLR has been reported previously in the Hutterite population and
in a family from Iran . However, quadrupedal locomation was never observed
indicating that environmental factors play a major role in the
pathogenesis of this form of locomotion .
P01.354
Old iranian scientists conception about reproduction and
Genetics were almost similar to modern Facts
M. H. Kariminejad;
Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Islamic Republic
of Iran.
The oldest scientific hypothesis in this regards is attributed to Hippocrates,
which denotes, that “man’s water (semen) is an extract from
the whole body and contains all the characteristics of the man” .
Aristotle believed that the semen originated from blood and gave life to
the clotted menstrual blood . In general, the scientists believed that all
characteristics were inherited only from the father . This belief persisted
for about 2000 years, until William Harvey, showed that there were no
traces of blood clots in the uterus of the pregnant hunted gazelles .
C .E . Wolf in the late 17 th century showed that the embryo is a product
of the fertilization of ovum by spermatozoid . It is surprising that based
on the Zoroastrian law the right of women and men were equal in all
respects .
The Zoroastrian priests, would pass, this important position to their
offspring regardless of the sex . Eight hundred years before Wolfs’ discovery
the sage Ferdowsi describes the royal characteristic of Kaykhosrow,
the grand son of the kings Kaykavoos and Afrasyab: “He, the
pure bred, has inherited from two races” .
More interesting, in the book written in the first half of the thirteenth
century, characteristics of the spermatozoid have been described in
an appealing way almost same as what we know today . Despite this
brilliant history, there was a big gap in this field between our country
and the developed world .
In spite of a long standstill, recently, we have moved to the front line
with our outstanding advancements in diagnosis, prevention and treatment
of hereditary diseases, particularly application of embryonic cells
in production and restoration of body organs and cloning of “Royana”,
which with all rewarding advancements, have placed our country
among pioneers and leaders of this caravan .
P01.355
mitochondriopathy presenting with immune disorder
I. Karačić 1 , A. Gagro 2 , R. Horvath 3 , M. Ćuk 1 , V. Sarnavka 4 , G. Tešović 5 , H.
Lochmuller 6 , N. Barišić 1,4 , M. Novak 4 , S. Galić 4 , M. Cvitković 4 , M. Jelušić 1,4 , M.
Vidović 4 , D. Begović 1,4 , L. Tambić-Bukovac 4 , I. Barić 1,4 ;
1 Zagreb University School of Medicine, Zagreb, Croatia, 2 Institute of Immunology,
Zagreb, Croatia, 3 Mitochondrial Research Group, University of Newcastle
upon Tyne, Newcastle upon Tyne, United Kingdom, 4 Department of Pediatrics,